This a competitive renewal application for the Cancer Center Support Grant (CCSG) of Roswell Park Cancer Institute (RPCI) for the grant period 2000-2005. This grant is entering its 25th year of uninterrupted funding. Over the last three years RPCI has achieved tremendous new changes in its governance, increased Institutional Commitment to staff recruitment (38 new faculty within the next three years), major renovation of program facilities, expanded philanthropic funding, reorganization of clinical and scientific departments, established interactive scientific and clinical translational programs, strengthened its administrative infrastructure, and enhanced its programmatic relationship with the University at Buffalo. Under the leadership of Dr. David Hohn, President and CEO, RPCI is well-positioned to take advantage of new opportunities and challenges. The Center seeks a significant increase in CCSG funding to match its expanded Institutional commitment. The total request of $3,039,144 will support six scientific programs (Therapeutics, Biophysical Therapies, Immunology, Mouse Molecular Genetics, Cancer Genetics), two disease-oriented programs (Gastrointestinal Oncology, Breast Cancer Research), a Cancer Prevention and Control Program, fourteen shared resources and three clinical support units. The requested support has increased from approximately $1.5 million to $3.0 million. The increase is distributed as follows: New shared resources (25%), increased utilization of existing shared resources. (17%), expansion of shared resources (11%), developmental funds), and requests for salary of senior and program leadership (29%). The funds will be used to support 182 CCSG full members have peer-reviewed funding. With the new leadership, improved environment for basic and translational research, and an increased Institute financial commitment to program development, RPCI is poised to make significant new advances in prevention, early detection, diagnosis and treatment of cancer over the next five years.